Biomarkers ID Teen-Onset Depression

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Note that early-onset major depressive disorder -- occurring in people under 25 years of age -- is a serious psychiatric condition with a poorer prognosis than adult onset.

Note also that this study was able to identify a group of 11 RNA transcripts in the blood of teens who fulfill the criteria for major depression that differentiated affected patients from controls with no history of depression.

A group of genetic biomarkers has been identified that are associated with early-onset major depression, suggesting the possibility of an objective blood test in the future, researchers reported.

A group of 11 RNA transcripts in the blood of teens who fulfill the criteria for major depression differentiated affected patients from controls with no history of depression, according to Eva E. Redei, PhD, of Northwestern University in Chicago, and colleagues.

In addition, 18 markers -- some overlapping with the major depression transcripts -- could distinguish individuals with depression with comorbid anxiety from those with depression alone, the researchers reported online in Translational Psychiatry.

The biomarkers they identified have various functions and gene products, but many are involved in neurodevelopment as well as degeneration, neural protection, and oxidative stress.

Major depression in adolescents appears to have a pronounced genetic component, and often is more difficult to treat than is depression in adults because of phenotypic heterogeneity.

The condition can have a significant impact on psychosocial development and is associated with persistent difficulties in adulthood such as substance abuse and suicidality.

"The benefit of having valid, reliable, selective and feasible biomarkers for [major depressive disorder] is clear, but despite 30 years of research we still do not have them," wrote Redei and colleagues.

With the goal of identifying potential markers that could ultimately be used clinically, her team first performed genome-wide expression analyses in blood and brain tissue of a rat model of depression, comparing the transcript results with results from control animals.

Out of hundreds of transcripts tested, seven were expressed in both blood and brain tissue of the animals, and three had particularly high expression in the brain.

The researchers also analyzed tissue from rats that had not been bred for depression, but had been exposed to chronic restraint stress, and selected 15 transcripts with significantly different expression than was seen in unstressed animals.

They next examined 26 corresponding genes in their patient cohort, which included 14 adolescents with major depressive disorder and 14 healthy controls.

Patients averaged 16 years old and were similar to controls in gender and race.

Their history of psychiatric disease was evaluated using the Diagnostic Interview Schedule for Children and Adolescents-IV, and exposure to stress was evaluated on the Childhood Trauma Questionnaire, which measures early life maltreatment.

Of the 26 candidate genes, 11 had significantly higher expression in the depressed adolescents.

Five of the gene candidates, ATP11C, CD59, IGSF4/CADM1, MAF, and RAPH1, had corresponded to genes in the genetic rat model.

The other six, AMFR, CAT, CDR2, CMAS, PSME1, and PTP4A3, corresponded to genes in the chronic stress animal model.

The researchers next assessed differences in effect size of gene expression for patients with depression alone and for depression with comorbid anxiety, and found 18 candidates.

Twelve of the candidate genes were specific to depression plus anxiety, the majority deriving from the chronic stress model.

These findings "support the longstanding clinical impression that [major depressive disorder] with comorbid anxiety disorders is a unique phenotype," the researchers observed.

The researchers next correlated patients' stress from maltreatment on the trauma questionnaire with the 26 candidate gene transcripts, and found that four showed an effect size of medium or greater.

All four, CMAS, PSME1, PTP4A3, and IRF3, corresponded to genes in the chronic stress model.

In discussing their findings, Redei and colleagues explained their rationale for using the two different animal models.

"These models comprised the genetic and the environmental (chronic stress) components of [major depressive disorder] etiology, and thereby these candidate biomarkers for [major depressive disorder] highlight genetic vulnerability factors and their transcriptomic consequences, in addition to biological costs of a repeated stressor," they wrote.

The study was limited by the small number of participants and reliance on animal models that reflect only some features of major depressive disorder.

This pilot study suggested that it may be possible to develop a panel of markers that could objectively diagnose major depression and to differentiate depression alone from depression accompanied by anxiety, according to the researchers.

"Eventually, the effect of treatment on validated biomarker panels can be established, allowing for further individual [major depressive disorder] treatment strategies," they predicted.

This research was supported by the Davee Foundation, the RD Foundation, the National Institutes of Health, and the Research Institute of Nationwide Children's Hospital in Columbus, Ohio.

The authors declared they had no conflicts of interest.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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